DESCRIPTION Endomorphin-2 (Tyr-Pro-Phe-NH2) is an endogenous morphine-like substance which binds to the mu opiate receptor with high affinity and selectivity. Endomorphin-2-like immunoreactivity has been demonstrated in the medulla and superficial layers of the dorsal horn in the spinal cord and in primary afferents (reprint enclosed), suggesting a role for this peptide in pain transmission. This program will test the hypothesis that endomorphin-2 is decreased in these areas after inflammation and chronic constriction injury. This reduction in endomorphin is postulated to produce a loss of inhibition of excitatory transmitters and contribute to the hyperalgesia known to occur in these pathological states. In Specific Aims 1 and 2, a unilateral inflammatory response or chronic constriction injury will be induced. Immunocytochemistry will be used to test the hypothesis that endomorphin-2-like immunoreactivity is reduced on the inflamed or injured side relative to the contralateral side and sham controls. Specific Aim 3 will examine the ability of exogenously administered endomorphin-2 to inhibit hyperalgesia and allodynia induced by administration of complete Freund's adjuvant (CFA).